Background and overview[1]
4-Chloro-3-fluorophenol is an organic intermediate. 4-amino-3-fluorophenol can be prepared from o-fluoronitrobenzene as raw material, and then acyl chlorination reaction can occur to prepare 4-chloro-3-fluorophenol. . 4-Chloro-3-fluorophenol can further prepare the pharmaceutical intermediate 4-chloro-3-fluoroanisole.
Preparation[1]
(1) Mix deionized water and absolute ethanol and add concentrated sulfuric acid dropwise. Finally, add o-fluoronitrobenzene and catalyst to the reaction kettle, seal the kettle, and introduce hydrogen into the reaction kettle until the pressure of the reaction kettle is 0.1-0.4MPa, then stir at 1000 rpm, while raising the temperature to 60°C, and increasing the pressure in the reactor to 0.4-0.6MPa, react for 1 hour, after the reaction is completed, cool to room temperature, filter, and obtain The filtrate was extracted three times with ethyl acetate. The organic phase obtained from the three extractions was collected and distilled under reduced pressure to obtain a crude product. The crude product was then recrystallized and dried with petroleum ether to obtain 4-amino-3-fluorophenol; 4-amino-3 -The purity of fluorophenol is 95.68%, and the yield is 80.3%; wherein, the catalyst is a porous silica-supported palladium-carbon composite catalyst; in the catalyst, the mass ratio of porous silica to palladium-carbon is 40:3; the catalyst and The mass ratio of o-fluoronitrobenzene is 1: 10;
(2) Using N,N-dimethylformamide as the reaction medium, 4-amino-3-fluorophenol and acid chloride reagent undergo acid chlorination reaction to prepare 4-chloro-3-fluorophenol.
Apply[1]
The preparation method of 4-chloro-3-fluorophenylethyl ether is as follows:
(1) Mix sodium phenolate and sodium hydroxide aqueous solution, then add 4-chloro-3-fluorophenol, stir and mix evenly to prepare a mixed solution; wherein, the sodium phenolate and 4-chloro-3-fluorophenol The molar ratio of phenol is 0.5:1; the mass concentration of the sodium hydroxide aqueous solution is 10%; the mass ratio of the sodium hydroxide aqueous solution and sodium phenolate is 10:1;
(2) Add the mixed solution prepared above into the reactor, then add diethyl sulfate, stir for 3 minutes, then raise the temperature to 80°C for reaction; after the reaction is completed, adjust the pH of the reaction system to 2- 5. Let stand for layering, collect the oil phase, then wash the oil phase with sodium hydroxide aqueous solution, and then collect the oil phase, which is 4-chloro-3-fluorophenylethyl ether, wherein the diethyl sulfate, 4- The molar ratio of chloro-3-fluorophenol is 0.5:1.
References
[1] [Chinese invention] CN201711040870.1 A preparation method of 4-chloro-3-fluorophene ethyl ether
